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| Status |
Public on Nov 12, 2021 |
| Title |
Sequence determinants of human gene regulatory elements, STARR-seq motif library experiments |
| Organisms |
Homo sapiens; synthetic construct |
| Experiment type |
Other
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| Summary |
DNA determines where and when genes are expressed, but the full set of sequence determinants that control gene expression is not known. Here, we measured transcriptional activity of DNA sequences that represent ~100 times larger sequence space than the human genome using massively parallel reporter assays. Machine learning models revealed that transcription factors (TFs) act generally in an additive manner with weak grammar, and that enhancers increase expression from a promoter by a mechanism that does not involve specific TF-TF interactions. The enhancers themselves can be classified into three distinct types: classical, closed chromatin and chromatin-dependent enhancers. We also show that few TFs are strongly active in a cell, with most activities similar between cell types. Individual TFs can have multiple gene regulatory activities, including chromatin opening, enhancing, promoting and TSS determining activity – consistent with the view that the TF binding motif is the only atomic unit of gene expression.
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| Overall design |
STARR-seq library containing known TF motifs with different orientations and spacings. Experiments done with two different plasmids, each having its own control.
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| Contributor(s) |
Sahu B, Hartonen T, Pihlajamaa P, Wei B, Dave K, Zhu F, Kaasinen E, Lidschreiber K, Lidschreiber M, Daub CO, Cramer P, Kivioja T, Taipale J |
| Citation(s) |
35190730 |
| Submission date |
Jul 15, 2021 |
| Last update date |
Feb 23, 2022 |
| Contact name |
Teemu Kivioja |
| Organization name |
University of Helsinki
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| Street address |
Haartmaninkatu 8
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| City |
Helsinki |
| ZIP/Postal code |
00014 |
| Country |
Finland |
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| Platforms (2) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
| GPL21616 |
Illumina HiSeq 4000 (synthetic construct) |
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| Samples (3) |
| GSM5454430 |
STARR-seq GP5d TF motifs library, pCpG-free- EF1alpha-SS vector |
| GSM5454431 |
STARR-seq GP5d TF motifs library, pGL4.10-Sasaki-SS vector |
| GSM5454432 |
STARR-seq TF motif input library, pCpG-free- EF1alpha-SS vector and pGL4.10-Sasaki-SS vector |
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| This SubSeries is part of SuperSeries: |
| GSE180158 |
Sequence determinants of human gene regulatory elements |
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| Relations |
| BioProject |
PRJNA746786 |
| SRA |
SRP328466 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE180151_STARR-seq_motif_library_GP5d_counts.lfc.tsv.gz |
1.4 Mb |
(ftp)(http) |
TSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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